The olfactory epithelium is unique in its ability to replace dying neurons throughout life. The basal cells are responsible for this regenerative capacity and can be divided in two groups, horizontal basal cells (HBCs) and globose based cells (GBCs). The GBCs are considered the immediate neuronal precursors that continually replace neurons that degenerate during normal daily exposure to the environment. These cells also respond to direct lesions of the epithelium, removal of their target organ, and olfactory nerve transection by increasing their rate of proliferation and production of neurons. The signals involved in triggering this increase in proliferation after neuronal degeneration are unknown. The HBCs serve as an intermediate signaling cell in the detection of neuronal degeneration and initiation of regeneration. In addition, HBCs possess epidermal growth factor (EGF) receptors that appear to the active during regeneration. The proposed experiments are designed to examine the relationship between EGF receptor activity of HBCs and the process of neuronal degeneration/regeneration. To address this issue, surgical transection of olfactory axons will be performed to initiate degeneration and regeneration of olfactory receptor neurons. Immunocytochemistry and olfactory epithelial explant cultures will also be utilized to examine this process. Understanding the mechanisms involved in regeneration have long term implications for reversing lesions to the nervous system.